A clinical trial for patients with high-grade neuroendocrine tumors is now open for enrollment at the Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.

High-grade neuroendocrine cancer is a complex and aggressive condition that has seen few medical advances, in part because its rarity has subdued research investment. Patients have few options beyond conventional chemotherapy.

The new trial, headed by Aman Chauhan, MD, leader of the Neuroendocrine Tumor Program at Sylvester, offers a fresh approach. Patients will receive a combination of immunotherapy drugs and a tumour-busting “oncolytic” virus injected directly into the tumours.

Tumours In Any Organ at Any Age

Neuroendocrine tumours originate from cells found throughout the body and can affect most organ systems. They most often attack the lungs, gastrointestinal tract, gynecological tract and prostate.

About one-sixth of neuroendocrine tumours are classified by pathologists as high grade. Survival rates from high-grade cancer vary with the site of disease, but most patients succumb within a year or two, said Dr. Chauhan. People older than 60 account for the majority of cases, but these aggressive tumours can strike people of any age.

Victims of high-grade disease include Sean Stone, an emerging Hollywood producer who passed away last March at only 26 years of age, and Nichole Borchard, a vibrant mother of two young children who died in September 2024 at age 39. Her family established the Nichole Borchard Foundation to honor the legacy of “an extraordinary woman who fought like hell to live and get better.” Stone’s family founded the Sean Stone’s Neuroendocrine Carcinoma Fundraiser, which supports research at Sylvester.

Checkpoint Inhibitors and “Hot” Tumours

In the new trial, Chauhan will combine immunotherapy drugs called checkpoint inhibitors with SVV-001 (Seneca Valley Virus-001), an oncolytic virus that has been tested for safety in previous trials.

Checkpoint inhibitors have broadened treatment options for a growing list of tumour types, from melanoma to lung cancer.

Very few high-grade neuroendocrine carcinomas respond to the drugs. But when they do, the effect is often long-lasting.

The challenge is to increase the number of patients who fully respond to immunotherapy.

That’s where Seneca Valley Virus comes in. SVV doesn’t infect normal cells. It grows inside tumour cells and busts them open. When the tumour cells burst, they release their contents, activating the immune system. The virus then goes on to infect other tumours and keeps the chain reaction going.

The checkpoint inhibitors, in turn, amp up the immune response against tumour components. In the trial, patients will receive the checkpoint inhibitors nivolumab and ipilimumab.

Chauhan and colleagues previously tested the approach in preclinical cancer models. The tumour shrank and yielded durable responses, he said.

In those studies, the oncolytic virus turned immune “cold” tumours into “hot” tumors that respond to checkpoint inhibitors. The drugs, in turn, acted like “fuel to the fire,” strengthening the attack against the tumour, said Chauhan.

Biomarker Boost

The new phase 1 trial will enroll about 36 people whose tumours have become resistant to or failed previous lines of therapy.

The aim is to find safe combination doses and to begin comparing effectiveness with historical data from standard-of-care treatment.

Patient tumours will also be tested for the presence of a new biomarker found on tumour cells called TEM8, which binds to the oncolytic virus. This phenomenon is unique to SVV and allows the virus to attach to cancer cells and infect them effectively. TEM-8 makes SVV a targeted immunotherapy drug.

Partners in Research and Care

In the past two years, more than 550 new patients from 30 different states and 10 different countries have come to Sylvester for treatment and access to neuroendocrine cancer clinical trials.

Chauhan heads several clinical trials for neuroendocrine tumours and carcinomas. This is his first investigator-initiated trial at Sylvester dedicated to high-grade neuroendocrine disease.